8,713 research outputs found

    Altered mitochondrial function and energy metabolism is associated with a radioresistant phenotype in oesophageal adenocarcinoma

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    Neoadjuvant chemoradiation therapy (CRT) is increasingly the standard of care for locally advanced oesophageal cancer. A complete pathological response to CRT is associated with a favourable outcome. Radiation therapy is important for local tumour control, however, radioresistance remains a substantial clinical problem. We hypothesise that alterations in mitochondrial function and energy metabolism are involved in the radioresistance of oesophageal adenocarcinoma (OAC). To investigate this, we used an established isogenic cell line model of radioresistant OAC. Radioresistant cells (OE33 R) demonstrated significantly increased levels of random mitochondrial mutations, which were coupled with alterations in mitochondrial function, size, morphology and gene expression, supporting a role for mitochondrial dysfunction in the radioresistance of this model. OE33 R cells also demonstrated altered bioenergetics, demonstrating significantly increased intracellular ATP levels, which was attributed to enhanced mitochondrial respiration. Radioresistant cells also demonstrated metabolic plasticity, efficiently switching between the glycolysis and oxidative phosphorylation energy metabolism pathways, which were accompanied by enhanced clonogenic survival. This data was supported in vivo, in pre-treatment OAC tumour tissue. Tumour ATP5B expression, a marker of oxidative phosphorylation, was significantly increased in patients who subsequently had a poor pathological response to neoadjuvant CRT. This suggests for the first time, a role for specific mitochondrial alterations and metabolic remodelling in the radioresistance of OAC

    Dispersion insensitive, high-speed optical clock recovery based on a mode-locked laser diode

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    An investigation into the effects of varying levels of chromatic dispersion on a mode- locked laser diode optical clock recovery process is presented. Results demonstrate that this technique is invariant to input dispersion varying between +75 ps/nm

    Fatigue Crack Detection Using Unmanned Aerial Systems in Under-Bridge Inspection

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    The applications of Unmanned Aerial Systems (UAS) for bridge inspection, with emphasis on under-bridge inspection and fatigue crack detection, were studied in this report. The potential benefits and challenges of using UAS for bridge inspection were identified through an extensive literature survey. The feasibility of using UAS for fatigue crack detection was studied by determining the minimum lighting, camera distance and environmental requirements for three UAS. The DJI Mavic UAS performed better than the others in both indoor and outdoor GPS-denied inspections. An in-service bridge in Ashton, Idaho was inspected using this UAS to find fatigue cracks. No fatigue crack, known or new, was detected in the UAS images but marker lines around the known fatigue cracks (drawn by the inspectors in previous inspections), concrete defects, and steel rust were detected. Thermography showed promising results for fatigue crack detection in a lab setting, but it was not feasible for UAS applications since it had to be performed using active thermography techniques to obtain adequate results. Additionally, image processing algorithms for autonomous detection of both concrete and fatigue cracks were successfully developed. These algorithms, especially for fatigue crack detection, require more images to perform better, but were demonstrated as feasible to aid in a real-time inspection

    The tropospheric gas composition of Jupiter's north equatorial belt (NH3, PH3, CH3D, GeH4, H2O) and the Jovian D/H isotropic ratio

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    The gas composition of the troposphere of Jupiter in the clearest regions of the North Equatorial Belt (NEB) was derived from the Voyager 1 IRIS data. The infrared spectrum for this homogeneous cloud free region was modeled to infer altitude profiles for NH3, PH3, GeH4 and H2O. The Profiles for NH3 and PH3 were found to be depleted in the upper troposphere but otherwise in agreement with their solar values at the 1 bar level. The mole fraction for CH3D was determined to be 3.5(+1.0 or -1.3) x 10 to the minus 7th power. The GeH4 mole fraction of 7+ or -2 x 10 to the minus 10th power at the 2 to 3 bar level is a factor of 10 lower than the solar value. The H2O mole fraction is approximately 1 x 0.00001 at the 2.5 bar level and is increasing to approximately 3 x 0.00001 at 4 bars where it is a factor of 30 lower than solar. Using IRIS infrared values for the mole fractions of CH3D and CH4 a value of D/H = 3.6(+1.0 or -1.4)x 0.00001 is derived. Assuming this Jovian D/H ratio is representative of the protosolar nebula, and correcting for chemical galactic evolution, yields a value of 5.5 - 9.0 x 0.00001 for the primordial D/H ratio and an upper limit of 1.8 to 2.4 x 10 to the minus 31st power cu cm for the present day baryon density

    Thermal emission spectroscopy of the middle atmosphere

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    The general objective of this research is to obtain, via remote sensing, simultaneous measurements of the vertical distributions of stratospheric temperature, ozone, and trace constituents that participate in the catalytic destruction of ozone (NO(sub y): NO, NO2, NO3, HNO3, ClONO2, N2O5, HNO4; Cl(sub x): HOCl), and the source gases for the catalytic cycles (H2O, CH4, N2O, CF2Cl2, CFCl3, CCl4, CH3Cl, CHF2Cl, etc.). Data are collected during a complete diurnal cycle in order to test our present understanding of ozone chemistry and its associate catalytic cycles. The instrumentation employed is an emission-mode, balloon-borne, liquid-nitrogen-cooled Michelson interferometer-spectrometer (SIRIS), covering the mid-infrared range with a spectral resolution of 0.020 cm(exp -1). Cryogenic cooling combined with the use of extrinsic silicon photoconductor detectors allows the detection of weak emission features of stratospheric gaseous species. Vertical distributions of these species are inferred from scans of the thermal emission of the limb in a sequence of elevation angles. The fourth SIRIS balloon flight was carried out from Palestine, Texas on September 15-16, 1986 with 9 hours of nighttime data (40 km). High quality data with spectral resolution 0.022 cm(exp -1), were obtained for numerous limb sequences. Fifteen stratospheric species have been identified to date from this flight: five species from the NO(sub y) family (HNO3, NO2, NO, ClONO2, N2O5), plus CO2, O3, H2O, N2O, CH4, CCl3F, CCl2F2, CHF2Cl, CF4, and CCl4. The nighttime values of N2O5, ClONO2, and total odd nitrogen have been measured for the first time, and compared to model results. Analysis of the diurnal variation of N2O5 within the 1984 and 1986 data sets, and of the 1984 ClONO2 measurements, were presented in the literature. The demonstrated ability of SIRIS to measure all the major NO(sub y) species, and therefore to determine the partitioning of the nitrogen family over a continuous diurnal cycle, is a powerful tool in the verification and improvement of photochemical modeling

    Watching movies unfold - a frame-by-frame analysis of the associated neural dynamics

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    Our lives unfold as sequences of events. We experience these events as seamless, although they are composed of individual images captured in between the interruptions imposed by eye blinks and saccades. Events typically involve visual imagery from the real world (scenes), and the hippocampus is frequently engaged in this context. It is unclear, however, whether the hippocampus would be similarly responsive to unfolding events that involve abstract imagery. Addressing this issue could provide insights into the nature of its contribution to event processing, with relevance for theories of hippocampal function. Consequently, during magnetoencephalography (MEG), we had female and male humans watch highly matched unfolding movie events composed of either scene image frames that reflected the real world, or frames depicting abstract patterns. We examined the evoked neuronal responses to each image frame along the time course of the movie events. Only one difference between the two conditions was evident, and that was during the viewing of the first image frame of events, detectable across frontotemporal sensors. Further probing of this difference using source reconstruction revealed greater engagement of a set of brain regions across parietal, frontal, premotor, and cerebellar cortices, with the largest change in broadband (1–30 Hz) power in the hippocampus during scene-based movie events. Hippocampal engagement during the first image frame of scene-based events could reflect its role in registering a recognizable context perhaps based on templates or schemas. The hippocampus, therefore, may help to set the scene for events very early on
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